Inhibition of RNase P cleavage by aminoglycosides
1999 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 96, no 11, 6155-6160 p.Article in journal (Refereed) Published
A number of aminoglycosides have been reported to interact and interfere with the function of various RNA molecules. Among these are 16S rRNA, the group I intron, and the hammerhead ribozymes. In this report we show that cleavage by RNase P RNA in the absence as well as in the presence of the RNase P protein is inhibited by several aminoglycosides. Among the ones we tested, neomycin B was found to be the strongest inhibitor with a Ki value in the micromolar range (35 microM). Studies of lead(II)-induced cleavage of RNase P RNA suggested that binding of neomycin B interfered with the binding of divalent metal ions to the RNA. Taken together, our findings suggest that aminoglycosides compete with Mg2+ ions for functionally important divalent metal ion binding sites. Thus, RNase P, which is an essential enzyme, is indeed a potential drug target that can be used to develop new drugs by using various aminoglycosides as lead compounds.
Place, publisher, year, edition, pages
1999. Vol. 96, no 11, 6155-6160 p.
tRNA precursors, tRNA processing
Medical and Health Sciences Natural Sciences
IdentifiersURN: urn:nbn:se:uu:diva-147829ISI: 000080527100046PubMedID: 10339557OAI: oai:DiVA.org:uu-147829DiVA: diva2:400913